Get your own Free Home PageURSODEOXYCHOLIC ACID (ACTIGALL)
Ursodeoxycholic acid (UDCA) has been used in chronic liver diseaes and can limit hepatocyte injury. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholeresis. It has recently been used in the management of chronic hepatitis, cirrhosis, post liver transplant rejection, graft -versus-host disease and acute viral hepatitis, where it not only relieves symptoms of cholestasis but also arrests ongoing hepatocyte necrosis.
According to a study reported at the American Gastroenterology Association Digestive Disease Week meeting in Washington in May 1997 (Treatment of chronic hepatitis C with interferon with or without ursodeoxycholic acid: a randomized prospective trial), combination therapy with UDCA plus interferon was no more effective than interferon monotherapy in inducing a biochemical response in previously untreated patients with chronic hepatitis C. UDCA was, however, useful in prolonging the sustained biochemical response of IFN therapy in this small pilot study.
Axcan( Schering's Canadian partner ) is continuing its development program to obtain FDA approval for other indications for URSO(R), including prevention of the recurrence of colorectal polyps, hypercholesterolemia, adjunctive therapy of hepatitis C, and non alcoholic steatohepatitis( NASH ).
INTERFERON AND URSODEOXYCHOLIC ACID COMBINED THERAPY IN THE TREATMENT OF CHRONIC VIRAL C HEPATITIS: RESULTS FROM A CONTROLLED RANDOMIZED TRIAL IN 80 PATIENTS.
Boucher E; Jouanolle H; Andre P; Ruffault A; Guyader D; Moirand R; Turlin B; Jacquelinet C; Brissot P; Deugnier Y; Clinique des Maladies du Foie, Hôpital Pontchaillou, Rennes, France. Hepatology, 1995 Feb, 21:2, 322-7
Because 70% to 75% of patients with chronic hepatitis C either do not respond to or relapse after interferon (IFN) therapy, and because ursodeoxycholic acid (UDCA) has been shown to reduce aminotransferase levels in patients with chronic hepatitis, we undertook a prospective controlled randomized trial of IFN (group I) versus IFN plus UDCA (group II) in 80 patients with chronic hepatitis C. IFN was administered in both groups for 6 months (3 to 5 million units [MU] three times a week), and in group II UDCA (10 mg/kg/d) was administered with IFN and then alone for 3 additional months. Response to therapy was defined as the normalization of alanine transaminase (ALT) levels.
The results showed that 6 months after cessation of IFN, 59% of responders had relapsed in group I but only 27% had relapsed in group II (P = .03). There was no difference between the two groups for the initial (month 6) and the late (months 15 and 18) response rates to IFN. There was no virological effect or significant histological improvement attributable to the addition of UDCA to IFN treatment. In conclusion, the results of this study show that the addition of UDCA to IFN therapy significantly prolongs the period for which serum ALT remain, within the normal range after discontinuation of IFN. Further studies would be required to determine whether UDCA has any potential for long-term amelioration of the histological severity of liver disease caused by hepatitis C virus (HCV) infection, and, therefore, whether it could be advocated as an adjunct to antiviral therapy
EFFECT OF LONG-TERM URSODEOXYCHOLIC ACID TREATMENT ON SERUM LIVER ENZYMES AND SERUM BILE ACID METABOLISM IN CHRONIC HEPATITIS
Nakamura K; Akiyama K; Makino I; Second Department of Internal Medicine, Asahikawa Medical College. Nippon Shokakibyo Gakkai Zasshi, 1995 Jan, 92:1, 62-71
The effect of ursodeoxycholic acid (UDCA) treatment for more than one year on chronic hepatitis in regard to responder and non-responder and influence of UDCA administration on serum bile acid metabolism were studied. All of non-responders (16 patients) were hepatitis B or C patients, and seven of fifteen responders were negative for hepatitis B and C virus marker and could be considered autoimmune hepatitis. These patients got drastic improvement of liver function test, anti-nuclear antibody in five patients and anti-smooth muscle antibody in three patients were decreased. Although HAI scores for liver pathology before UDCA treatment were not different between responders and non-responders, the intralobular necrosis was improved in responders after UDCA treatment. Concerning serum bile acid analysis, total bile acid and UDCA concentration in responders were lower than non-responders. Percentage of iso-ursodeoxycholic acid in responders was significantly higher than non-responders. These results suggest the effectiveness of UDCA therapy on autoimmune hepatitis.
TWO CASES FROM THE SPECTRUM OF NONALCOHOLIC STEATOHEPATITIS
Abdelmalek M; Ludwig J; Lindor KD; Division of Gastroenterology and Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. (J Clin Gastroenterol, 1995 Mar)
Nonalcoholic steatohepatitis is a poorly understood disease that mimics alcoholic liver disease histologically. Its natural history is not well defined, although gradual progression to cirrhosis has been described. Most patients with this condition have been obese, with or without associated diabetes or hyperlipidemia. No known effective treatment exists for nonalcoholic steatohepatitis, although weight loss may have a beneficial effect. We report two cases of nonalcoholic steatohepatitis. One patient with well-established nonalcoholic steatohepatitis had cirrhosis with a complete loss of fat on subsequent liver biopsy despite a gain in weight, simulating cryptogenic cirrhosis. In another patient, the condition improved after use of URSODEOXYCHOLIC ACID; this agent may be a potential therapeutic agent for the treatment of nonalcoholic steatohepatitis. We believe these two cases represent the spectrum of this condition: on the one end is a progressive liver disease that in some instances may be a cause of cryptogenic cirrhosis; at the other end, a potentially treatable liver condition.
URSODEOXYCHOLIC ACID IN THE TREATMENT OF CHOLESTASIS OF PREGNANCY
Joaquín Palma, Humberto Reyes, José Ribalta, Ismael Hernández, Lorena Sandoval, Ramón Almuna, Juris Liepins, Fernando Lira, Manuel Sedano, Octavio Silva, Dolores Tohá and Juan Jorge Silva; Journal of Hepatology, December 1997, Volume 27, Issue 6, Page 1022-1028
Background/Aims: Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset.
Methods: Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery.
Results: Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mothers or in their babies. After 3 weeks of treatment, patients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), in serum bilirubin (0.36±0.19 mg/dl (mean±SD) versus 0.95±0.48 in patients receiving placebo, p<0.01), in aspartate aminotransferase (52±42 IU/l vs 98±44, p<0.05) and in alanine aminotransferase (54±50 IU/l vs 229±154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3±33.7 µmol/l vs 55.0±44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery.
Conclusions: Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.
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